Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires

Improving limb salvage in critical ischemia with intermittent pneumatic compression: A controlled study with 18-month follow-up

BackgroundIntermittent pneumatic compression (IPC) is an effective method of leg inflow enhancement and amelioration of claudication in patients with peripheral arterial disease. This study evaluated the clinical efficacy of IPC in patients with chronic critical limb ischemia, tissue loss, and nonhealing wounds of the foot after limited foot surgery (toe or transmetatarsal amputation) on whom additional arterial revascularization had been exhausted.MethodsPerformed in a community and multidisciplinary health care clinic (1998 through 2004), this retrospective study comprises 2 groups. Group 1 (IPC group) consisted of 24 consecutive patients, median age 70 years (interquartile range [IQR], 68.7-71.3) years, who received IPC for tissue loss and nonhealing amputation wounds of the foot attributable to critical limb ischemia in addition to wound care. Group 2 (control group) consisted of 24 consecutive patients, median age 69 years (IQR, 65.7-70.3 years), who received wound care for tissue loss and nonhealing amputation wounds of the foot due to critical limb ischemia, without use of IPC. Stringent exclusion criteria applied. Group allocation of patients depended solely on their willingness to undergo IPC therapy. Vascular assessment included determination of the resting ankle-brachial pressure index, transcutaneous oximetry (TcPO2), duplex graft surveillance, and foot radiography. Outcome was considered favorable if complete healing and limb salvage occurred, and adverse if the patient had to undergo a below knee amputation subsequent to failure of wound healing. Follow-up was 18 months. Wound care consisted of weekly débridement and biologic dressings. IPC was delivered at an inflation pressure of 85 to 95 mm Hg, applied for 2 seconds with rapid rise (0.2 seconds), 3 cycles per minute; three 2-hourly sessions per day were requested. Compliance was closely monitored.ResultsBaseline differences in demography, cardiovascular risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia, renal impairment), and severity of peripheral arterial disease (ankle-brachial indices, TcPO2, prior arterial reconstruction) were not significant. The types of local foot amputation that occurred in the two groups were not significantly different. In the control group, foot wounds failed to heal in 20 patients (83%) and they underwent a below knee amputation; the remaining four (17%, 95% confidence interval [CI], 0.59%-32.7%) had complete healing and limb salvage. In the IPC group, 14 patients (58%, 95% CI, 37.1%-79.6%) had complete foot wound healing and limb salvage, and 10 (42%) underwent below knee amputation for nonhealing foot wounds. Wound healing and limb salvage were significantly better in the IPC group (P < .01, χ2). Compared with the IPC group, the odds ratio of limb loss in the control group was 7.0. On study completion, TcPO2 on sitting was higher in the IPC group than in the control group (P = .0038).ConclusionIPC used as an adjunct to wound care in patients with chronic critical limb ischemia and nonhealing amputation wounds/tissue loss improves the likelihood of wound healing and limb salvage when established treatment alternatives in current practice are lacking. This controlled study adds to the momentum of IPC clinical efficacy in critical limb ischemia set by previously published case series, compelling the pursuit of large scale multicentric level 1 studies to substantiate its actual clinical role, relative indications, and to enhance our insight into the pertinent physiologic mechanisms

Quasi-Seeded Growth of Ligand-Tailored PbSe Nanocrystals through Cation-Exchange-Mediated Nucleation

We present deep CCS and HC_7N observations of the L1495-B218 filaments in the Taurus molecular cloud obtained using the K-band focal plane array on the 100 m Green Bank Telescope. We observed the L1495-B218 filaments in CCS J_N = 2_1–1_0 and HC_7N J = 21−20 with a spectral resolution of 0.038 km s^(−1) and an angular resolution of 31''. We observed strong CCS emission in both evolved and young regions and weak emission in two evolved regions. HC_7N emission is observed only in L1495A-N and L1521D. We find that CCS and HC_7N intensity peaks do not coincide with NH_3 or dust continuum intensity peaks. We also find that the fractional abundance of CCS does not show a clear correlation with the dynamical evolutionary stage of dense cores. Our findings and chemical modeling indicate that the fractional abundances of CCS and HC_7N are sensitive to the initial gas-phase C/O ratio, and they are good tracers of young condensed gas only when the initial C/O is close to solar value. Kinematic analysis using multiple lines, including NH_3, HC_7N, CCS, CO, HCN, and HCO^+, suggests that there may be three different star formation modes in the L1495-B218 filaments. At the hub of the filaments, L1495A/B7N has formed a stellar cluster with large-scale inward flows (fast mode), whereas L1521D, a core embedded in a filament, is slowly contracting because of its self-gravity (slow mode). There is also one isolated core that appears to be marginally stable and may undergo quasi-static evolution (isolated mode)

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires

The specification of ethnic cleavages and ethnopolitical groups for the analysis of democratic competition in contemporary Africa

Ethnicity remains an important (but not the only) cost‐effective strategic resource for organizing collective political action in Africa\u27s emerging democracies. To advance systematic analysis of the impact of ethnicity on current patterns of democratic politics and the potential for democratic consolidation, this article describes and presents a comprehensive data set on ethnopolitical groups in all 48 African countries. It explicates the theoretical orientation that informs the data set and the methodology used in defining, identifying and coding ethnopolitical groups